Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

Clustering of molecules on biological membranes is a widely observed
phenomenon. In some cases, such as the clustering of Ras proteins on the
membranes of mammalian cells, proper cell signaling is critically dependent on
the maintenance of these clusters. Yet, the mechanism by which clusters form
and are maintained in these systems remains unclear. Recently, it has been
discovered that activated Ras promotes further Ras activation. Here we show
using particle-based simulation that this positive feedback is sufficient to
produce persistent clusters of active Ras molecules at the nanometer scale via
a dynamic nucleation mechanism. Furthermore, we find that our cluster
statistics are consistent with experimental observations of the Ras system.
Interestingly, we show that our model does not support a Turing regime of
macroscopic reaction-diffusion patterning, and therefore that the clustering we
observe is a purely stochastic effect, arising from the coupling of positive
feedback with the discrete nature of individual molecules. These results
underscore the importance of stochastic and dynamic properties of reaction
diffusion systems for biological behavior.